Considerations in Demonstrating Interchangeability
with a Reference Product; Guidance for Industry
Comments Submitted by HOPA
1
April 17, 2017
Stephen Ostroff, M.D.
Acting Commissioner
U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
Re: Considerations in Demonstrating Interchangeability with a Reference Product; Guidance for Industry
Dear Dr. Ostroff:
On behalf of the Hematology/Oncology Pharmacy Association (HOPA), we are pleased with the direction provided by the Food and Drug Administration (FDA) to industry within this guidance and appreciate the opportunity to submit comments and feedback from our perspective as healthcare providers. We commend the thought and detail that went into the preparation of this guidance document.
HOPA is a non-profit professional organization launched in 2004 to help hematology and oncology pharmacy practitioners and their associates provide the best possible cancer care. HOPA’s membership includes not only oncology pharmacists, but also pharmacy interns, residents, technicians, researchers, and administrators that specialize in hematology/oncology practice. The roles of our membership span from direct patient care, to education, and research. HOPA represents more than 2,500 members that work in hundreds of hospitals, clinics, physician offices, community pharmacies, home health practices, and other healthcare settings.
Specifically, our role with the use of biosimilar drugs is to: (1) educate other healthcare professionals and patients pertaining to their appropriate use, (2) lead the discussion in most institutions where the use of biosimilar drugs are being considered for formulary addition, (3) develop guidelines for appropriate use within our patient population, (4) ensure that restrictions for use, or required interchange, if any, are met in the process of dispensing the drugs, and (5) monitoring patients to determine if unexpected or untoward reactions have occurred and ensure they are properly documented and reported. Our comments are designed to facilitate these responsibilities.
Quality Attributes
HOPA agrees with the FDA’s focus on defining quality attributes. It is important to know the exact quality attributes for each drug, for purposes of monitoring the effect and impact on our patients. Further, when differences are allowed between the reference drug and the biosimilar drug, it is important to know exactly what those differences are, why they exist, and how they will be measured. The guidance indicates that the molecular complexity will be the determining factor as to what criteria is required and how it will be measured. Therefore, HOPA would like the FDA to provide justification for the criteria and standards for each drug defined when the approval (or disapproval) is announced.
StudyDesign and Endpoints
HOPA supports the reliance on pharmacokinetics and pharmacodynamics (PK/PD) data versus efficacy, considering efficacy can be extrapolated provided the molecules are similar in structure, pharmacokinetics, and pharmacodynamics. Subtle differences in molecular structure could cause differences in PK/PD and should be studied prior to approval and monitored after approval if significant. Overall, HOPA agrees that this streamlined approach will be less costly, and would decrease approval time.
HOPA agrees that immunogenicity study criteria should be based on the tendency for a certain molecular class, determined by experience with the reference drug. The tendency for a complex protein based drug to stimulate the development of antibodies (Ab) should be monitored and reported for all drugs after they are approved for market use, and this generally becomes the responsibility of pharmacists in institutional practices. HOPA recommends that the FDA define the risk of immunogenicity, and the strategy used to measure the risk compared to the reference molecule at the time of approval of each drug to facilitate practitioners monitoring the drug in practice.
The guidance document at times mentions seemingly conflicting positions. HOPA recommends that the FDA include the following statement at the beginning of the interchangeability guidance: “the biosimilar drug in this application was assessed by and meets the same criteria as the reference drug, unless otherwise stated.” In those cases where differences exist, the FDA should state why, and explain how the different data resulted in approval or denial of the 351k application.
The clinical indications approved for the biosimilar is not clear as to whether the biosimilar can be interchangeable for all indications of the reference drug or not: For example:
Lines 76-79 state… “expects that sponsors will submit data and information to support a showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in all of the reference product’s licensed conditions of use.”;
Lines 114-119 state … “standard will likely not involve additional clinical studies other than those necessary to support other elements of 115 demonstrating interchangeability. We note that although a sponsor may seek licensure for a 116 proposed interchangeable product for fewer than all conditions of use for which the reference 117 product is licensed, we recommend that a sponsor seek licensure for all of the reference 118 product’s licensed conditions of use when possible.”; and
Lines 495-508 state… “sponsors should consider choosing a condition of use that would support subsequent extrapolation of data to other conditions of use.”
HOPA recommends that the FDA allow: (1) the same indications as the reference drug through extrapolation, for drugs approved under 351k; and (2) once approved, the sponsor is allowed to submit additional data or justification to extrapolate to other new indications earned by the reference product.
HOPA agrees with the criteria presented for switching studies. We wish to reinforce that wash out periods may not be feasible for patients in current therapy that requires a sustained minimum drug level. HOPA recommends that once interchangeability is determined between the reference drug and the similar drug, interchangeability be allowed between all biosimilar drugs approved using the same reference drug.
Presentation
HOPA supports the importance of the final dosage form and presentation being the same as the reference drug, to support safety and minimize drug errors. HOPA supports ensuring that the drug be provided in the same concentration, label description, diluent, vial and stopper material as the reference.
HOPA recommends that if the biosimilar manufacturer can provide supportive data that meets standards set by the FDA under 351a and other rules appropriate for the application, that the manufacture be allowed to apply for additional presentations (such as auto-injector, or ready to use vial) if they enhance drug delivery and improve access to care.
HOPA believes that the presentation of the drug also involves the naming of the drug. Considering that there may be differences in the criteria used to approve the drug, differences in approved indications, and differences in immunogenicity, it is important to have a name that allows providers to differentiate which drug they are actually using, or switching to. HOPA reinforces our previous recommendation that the drug name consist of the reference drug International Nonproprietary Name (INN) plus a meaningful suffix. We believe that the current FDA position of using the drug INN plus a random suffix is confusing and unsafe.
HOPA greatly appreciates the opportunity to share our comments on interchangeability draft guidance. We look forward to continuing to work with the FDA and the new administration on implementation of this important issue. Should you have any questions, please do not hesitate to contact our Health Policy Associate, Jeremy Scott (202/230-5197, ). We thank you for your consideration of these comments and recommendations.
Sincerely,
Susannah Koontz, PharmD BCOP FHOPA
President
Hematology/Oncology Pharmacy Association